Chlamydia trachomatis is the leading bacterial sexually transmitted disease. An effective vaccine would be one of the best strategies for control of chlamydia. However, efforts to develop a chlamydia vaccine have been unsuccessful so far. Despite these failures, the available epidemiological data suggest that natural chlamydia infection is followed by short-term protective immunity and, on this basis, development of a vaccine should be feasible. The problem at this juncture is to define the nature of the protective response. One of the major difficulties impeding the definition of epitopes that might mediate protection is the lack of well characterized immunological reagents. One goal of this project is to develop assays to identify antibodies to specific chlamydial gene products by using as antigens either labeled proteins translated in vitro from chlamydial genes that have already been cloned and sequenced, or synthetic peptides which are known to represent serovar-specific epitopes on the major outer membrane protein (MOMP). These reagents will be used to characterize anti-chlamydial response in serum and genital secretion. Most previous methods for measuring antigen-specific IgA in body fluids have not used reagents that detect the secretary component of IgA, nor have they been performed in a way that would eliminate interference by IgG which is also found in body fluids. To address this problem, we will develop methods to assay specific SigA in genital secretions by using a mouse monoclonal antibody specific for secretory IgA. To remove IgG, specimens will be immunoprecipitated. The epidemiological investigations have two principal aims. First, we will determine the antibody prevalence to genital strains of C. trachomatis in populations with different risk of prior STD (STD clinic patients, college-age men and women, girls and boys seen in an adolescent medicine clinic, and healthy children). Second, a nested case-control study will be performed in the Baltimore City STD Clinics in order to evaluate serum and local antibody markers as predictors of reduced risk of chlamydial infection. Serum and genital secretions will be collected prospectively on all clinic attendees. Cases (infected women) and controls (a random sample of uninfected women or uninfected women who are known, through contact tracing, to have been exposed to chlamydia) will be identified and the sepciemn bank will be accessed. The antibody reactivity of cases and controls will be compared to identify serovar-specific or species-specific antibodies which are predictors of reduced risk of infection. A better understanding of the contribution of individual chlamydial antigens to the human immune response to chlamydia and identification of serologic markers that correlate with protection against chlamydial infection should assist in vaccine development efforts.